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MetaCyc Pathway: nicotinate degradation III
Traceable author statement to experimental supportInferred from experiment

Pathway diagram: nicotinate degradation III

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/AssimilationAromatic Compounds DegradationNicotinate Degradation

Some taxa known to possess this pathway include : Eubacterium barkeri

Expected Taxonomic Range: Firmicutes

Nicotinate (niacin, vitamin B3, 3-pyridinecarboxylate) is a pyridine ring-containing compound. Microorganisms have multiple ways of degrading pyridine and its derivatives, and degradation of these compounds is relevant to both biological and industrial processes. The degradation of nicotinate by both aerobic and anaerobic organisms involves the initial formation of 6-hydroxynicotinate, but the pathways diverge after that. Among aerobic organisms, the pathways in Pseudomonas and Bacillus niacini are shown in MetaCyc pathways nicotinate degradation I, and nicotinate degradation II, respectively. An anaerobic pathway for nicotinate degradation in Eubacterium barkeri (previously knowns as Clostridium barkeri) is shown here ( [Stadtman72] and reviewed in [Kaiser96, Berry87, Eggerer85]). This anaerobic fermentation pathway results in the formation of equimolar amounts of propionate, acetate, carbon dioxide and ammonia [Stadtman72]. The acetate and carbon dioxide are thought to be derived from pyruvate [Kung71a], as indicated by the pathway link.

The first reaction is ring hydroxylation, resulting in the formation of 6-hydroxynicotinate (sometimes shown in its 6-oxo tautomeric form) [Berry87, Stadtman72]. The next reaction is ring reduction. The following three reactions have been elucidated by the discovery of two chiral intermediates and three enzymes [Alhapel06]. These investigators also cloned the entire gene cluster encoding the nicotinate fermentation enzymes in Eubacterium barkeri. The enamidase is a bifunctional hydrolase that produces the chiral 2-formylglutarate and ammonia. This compound is then reduced to the chiral (S)-2-hydroxymethylglutarate. The next reaction is probably catalyzed by the product of gene hmd, predicted to be 2-(hydroxymethyl)glutarate dehydratase based on amino acid sequence similarity to bacterial [4Fe-4S]-containing serine dehydratases [Alhapel06]. A vitamin B12 coenzyme-dependent mutase catalyzes a key rearrangement to form 2-methylene-3-methylsuccinate (methylitaconate). A reaction involving double bond migration results in the formation of dimethylmaleate. Hydration and cleavage reactions produce propionate and pyruvate. There is evidence that degradation of pyruvate via a ferredoxin-linked process, with acetyl-CoA and acetyl phosphate intermediates, results in ATP generation and the formation of acetate and carbon dioxide [Kung71a, KollmannKoch84]. Reviewed in [Kaiser96, Eggerer85].

Superpathways: superpathway of nicotinate degradation

Variants: nicotinate degradation I, nicotinate degradation II

Created 01-Dec-2005 by Fulcher CA, SRI International
Revised 09-Jan-2008 by Fulcher CA, SRI International


Alhapel06: Alhapel A, Darley DJ, Wagener N, Eckel E, Elsner N, Pierik AJ (2006). "Molecular and functional analysis of nicotinate catabolism in Eubacterium barkeri." Proc Natl Acad Sci U S A 103(33);12341-6. PMID: 16894175

Berry87: Berry DF, Francis AJ, Bollag JM (1987). "Microbial metabolism of homocyclic and heterocyclic aromatic compounds under anaerobic conditions." Microbiol Rev 51(1);43-59. PMID: 3550408

Eggerer85: Eggerer H (1985). "Completion of the degradation scheme for nicotinic acid by Clostridium barkeri." Curr Top Cell Regul 26;411-8. PMID: 4075828

Kaiser96: Kaiser JP, Feng Y, Bollag JM (1996). "Microbial metabolism of pyridine, quinoline, acridine, and their derivatives under aerobic and anaerobic conditions." Microbiol Rev 60(3);483-98. PMID: 8840783

KollmannKoch84: Kollmann-Koch A, Eggerer H (1984). "Nicotinic acid metabolism. Dimethylmaleate hydratase." Hoppe Seylers Z Physiol Chem 365(8);847-57. PMID: 6489933

Kung71a: Kung H, Tsai L, Stadtman TC (1971). "Nicotinic acid metabolism. 8. Tracer studies on the intermediary roles of -methyleneglutarate, methylitaconate, dimethylmaleate, and pyruvate." J Biol Chem 246(21);6444-51. PMID: 4332128


Stadtman72: Stadtman ER, Stadtman TC, Pastan I, Smith LD (1972). "Clostridium barkeri sp. n." J Bacteriol 110(2);758-60. PMID: 4553843

Tsai71: Tsai L, Stadtman ER (1971). "Anaerobic degradation of nicotinic acid." Methods Enzymol. 18:233-249.

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Beatrix94: Beatrix B, Zelder O, Linder D, Buckel W (1994). "Cloning, sequencing and expression of the gene encoding the coenzyme B12-dependent 2-methyleneglutarate mutase from Clostridium barkeri in Escherichia coli." Eur J Biochem 221(1);101-9. PMID: 8168499

Dilworth83: Dilworth GL (1983). "Occurrence of molybdenum in the nicotinic acid hydroxylase from Clostridium barkeri." Arch Biochem Biophys 221(2);565-9. PMID: 6838209

Gladyshev94: Gladyshev VN, Khangulov SV, Stadtman TC (1994). "Nicotinic acid hydroxylase from Clostridium barkeri: electron paramagnetic resonance studies show that selenium is coordinated with molybdenum in the catalytically active selenium-dependent enzyme." Proc Natl Acad Sci U S A 91(1);232-6. PMID: 8278371

Gladyshev96: Gladyshev VN, Khangulov SV, Stadtman TC (1996). "Properties of the selenium- and molybdenum-containing nicotinic acid hydroxylase from Clostridium barkeri." Biochemistry 35(1);212-23. PMID: 8555176

Holcenberg69: Holcenberg JS, Stadtman ER (1969). "Nicotinic acid metabolism. 3. Purification and properties of a nicotinic acid hydroxylase." J Biol Chem 244(5);1194-203. PMID: 4388026

Holcenberg69a: Holcenberg JS, Tsai L (1969). "Nicotinic acid metabolism. IV. Ferredoxin-dependent reduction of 6-hydroxynicotinic acid to 6-oxo-1,4,5,6-tetrahydronicotinic acid." J Biol Chem 244(5);1204-11. PMID: 5767303

Kung71: Kung HF, Stadtman TC (1971). "Nicotinic acid metabolism. VI. Purification and properties of alpha-methyleneglutarate mutase (B 12-dependent) and methylitaconate isomerase." J Biol Chem 246(10);3378-88. PMID: 5574401

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Michel89: Michel C, Hartrampf G, Buckel W (1989). "Assay and purification of the adenosylcobalamin-dependent 2-methyleneglutarate mutase from Clostridium barkeri." Eur J Biochem 184(1);103-7. PMID: 2776761

Michel91: Michel C, Buckel W, Linder D (1991). "Purification of the coenzyme B12-containing 2-methyleneglutarate mutase from Clostridium barkeri by high-performance liquid chromatography." J Chromatogr 587(1);93-9. PMID: 1783665

Michel91a: Michel C, Buckel W (1991). "Coenzyme B12-dependent 2-methyleneglutarate mutase from Clostridium barkeri. Protection by the substrate from inactivation by light." FEBS Lett 281(1-2);108-10. PMID: 2015880

Park06: Park YJ, Yoo CB, Choi SY, Lee HB (2006). "Purifications and characterizations of a ferredoxin and its related 2-oxoacid:ferredoxin oxidoreductase from the hyperthermophilic archaeon, Sulfolobus solfataricus P1." J Biochem Mol Biol 39(1);46-54. PMID: 16466637

Pierik05: Pierik AJ, Ciceri D, Lopez RF, Kroll F, Broker G, Beatrix B, Buckel W, Golding BT (2005). "Searching for intermediates in the carbon skeleton rearrangement of 2-methyleneglutarate to (R)-3-methylitaconate catalyzed by coenzyme B12-dependent 2-methyleneglutarate mutase from Eubacterium barkeri." Biochemistry 44(31);10541-51. PMID: 16060663

Pirzer79: Pirzer P, Lill U, Eggerer H (1979). "Nicotinic acid metabolism. 2,3-Dimethylmalate lyase." Hoppe Seylers Z Physiol Chem 360(12);1693-702. PMID: 527937

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Mon May 2, 2016, biocyc13.